1. Technical Field
The present disclosure relates to a blood analysis apparatus which centrifugally rotates a μ-TAS (Micro-Total Analysis System) chip for holding a sample, such as blood, and measures a measurement liquid held by the μ-TAS chip by an absorbance analysis method, and a setting method of a measurement position in the blood analysis apparatus. More particularly, the present disclosure relates to a blood analysis apparatus and a setting method of a measurement position in the blood analysis apparatus, which can exactly set the measurement position when the absorbance measurement of the measurement liquid held by the μ-TAS chip is performed.
2. Related Art
In recent years, attention is paid to an analytical method utilizing a μ-TAS chip, called “μ-TAS” or “Lab on a chip”, capable of applying a micro-machine technique and performing chemical analysis or the like in a finer manner as compared with a conventional apparatus.
The analyzing system (hereinafter referred to as “μ-TAS chip analyzing system”) using such a μ-TAS chip is a system which aims to perform all the steps of analysis including mixing, reaction, separation, extraction, and detection of a reagent in a fine flow passage formed on a small base through a micro-machine manufacturing technique, and is used for, for example, analysis of blood, and analysis of biomolecule, such as an ultratrace amount of protein or nucleic acid, in a medical field.
Particularly, when people's blood is analyzed using the μ-TAS chip analyzing system, the following advantages are obtained. Therefore, in recent years, development is positively moving forward.
(1) Since the amount of blood (sample) which is required for analytical inspection is slight amount, a burden to a patient can be mitigated.
(2) Since the amount of a reagent which is used while being mixed with blood is small, analysis cost can be reduced.
(3) Since the apparatus itself can be configured as a small one, analysis can be easily performed.
In such a μ-TAS chip analyzing system, for example, absorptiometry is used as a method for measuring the concentration of a component of an object to be detected in a measurement liquid (sample liquid). For example, JP-A-2007-322208 describes a blood analysis apparatus using the absorptiometry.
A configuration example of a measuring unit in the blood analysis apparatus is shown in FIG. 18. FIG. 18 is a schematic cross-sectional view showing the internal structure of the measuring unit in the blood analysis apparatus.
The blood analysis apparatus include a casing (not shown), and the inside of the casing is provided with a measuring unit 20, a light source unit having a light source 41, a light-receiving unit 43 (shown in FIG. 18), a controller, a power supply unit (not shown), and the like.
The measuring unit 20, as shown in FIG. 18, has a hollow columnar measuring chamber 21, and, for example, a cylindrical rotary body 25 having a bottom surface is arranged in the measuring chamber 21. A driving shaft 24b is arranged so as to extend in a vertical direction through a central position of the bottom surface of the rotary body 25, and the driving shaft 24b is connected to a centrifugal motor 24a. As the centrifugal motor 24a is driven, the rotary body 25 is rotationally driven.
The centrifugal motor 24a, the driving shaft 24b, and an encoder 24c (described later) constitute a rotation driving mechanism 24.
The bottom of the rotary body 25 is provided with a direction switching gear 26 whose external diameter is smaller than the radius of the rotary body 25, the direction switching gear 26 is rotatably supported around a shaft D which is located on the rotary body 25 and is parallel to the rotation center C thereof, and a chip holding portion 22 for holding a μ-TAS chip 60 is provided on the gear 26. The chip holding portion 22 is arranged so as to be located in an outer peripheral area of the rotary body 25.
In addition, the measuring unit 20 can be configured so as to have a plurality of the chip holding portions 22. In FIG. 18, in order to maintain the rotation balance of the rotary body 25 in a proper state, the chip holding portions 22 of the same configuration are provided in opposite positions with the rotation center C therebetween.
A light-introducing opening 22a and an aperture 23 which introduce the light incident via a reflecting mirror 42 from the light source 41 into a measuring area of the μ-TAS chip 60 are each formed at a lower portion of the measuring chamber 21, the rotary body 25, and the direction switching gear 26 provided with the chip holding portion 22, in a state that the μ-TAS chip 60 is held by the chip holding portion 22. A light-receiving unit 43 which receives this light which has passed through a measuring area of the μ-TAS chip 60 and an opening 22b in which an optical fiber 44 which guides the light is provided are provided in an upper portion of the measuring chamber 21.
When absorbance measurement of a measurement liquid within the measuring area of the μ-TAS chip 60 is performed, this measurement is performed in a state where the rotation of the rotary body 25 has been stopped, and it is necessary to introduce the light from the light source 41 into the measuring area of the μ-TAS chip 60. Accordingly, the stop position of the rotary body 25 must be controlled with high precision of position.
For this reason, the encoder 24c is connected to the centrifugal motor 24a for rotationally driving the rotary body 25, and the stop position of the rotary body 25 is controlled on the basis of a signal from the encoder 24c. 
Additionally, a planar heating means (heater) 35 for maintaining the temperature within the measuring chamber 21 at a constant temperature, for example, 37° C., at the time of analytical inspection, is provided in some regions of the top and bottom faces of the measuring chamber 21, and the temperature within the measuring chamber is controlled so as to become constant on the basis of the detection temperature by a temperature measuring means 36 such as a thermistor.
Additionally, the measuring unit 20 includes a chip direction switching mechanism 30, having a drive mechanism separate from a drive mechanism 24 which rotationally drives the rotary body 25. The chip direction switching mechanism 30 adjusts the direction of the μ-TAS chip 60 held by the chip holding portion 22.
The chip direction switching mechanism 30 has a driving-side gear 33 and a chip direction switching motor 31. The driving-side gear 33 is rotatably provided with respect to the driving shaft 24b of the centrifugal motor 24a via a ball bearing 32 or the like and meshes with the direction switching gear 26, and the chip direction switching motor 31 is a driving source for rotationally driving the driving-side gear 33.
By driving the chip direction switching motor 31, the driving-side gear 33 rotates, then the direction switching gear 26 which meshes with this gear rotates, and then the chip holding portion 22 rotates. This makes it possible to switch the direction (direction with respect to the rotation center C of the rotary body 25) of the μ-TAS chip 60.
For example, JP-A-2006-110491 describes the concrete structure, operation, etc. of the chip direction change mechanism 30.
Analytical processing of the measurement liquid by the above-described blood analysis apparatus is performed, for example, as follows. A rotary body mounted with the μ-TAS chip by which a sample (blood) is held is rotated, separation treatment which centrifugally separates the sample is performed using a centrifugal force, and a sample liquid obtained by the separation treatment is weighed.
Subsequently, pretreatment operation including mixing reaction treatment, in which the liquid to be measured and a reagent are mixed together to be reacted, and the processing of delivering a measurement liquid obtained by the mixing reaction treatment to a measuring area is performed.
Subsequently, while the rotation of the rotary body 25 is stopped, the light from the light source unit 41 is introduced into the measuring area of the μ-TAS chip 60, and the light transmitted through the measuring area is received by the light-receiving unit. Thereby, the quantity of light absorbed by the measurement liquid within the measuring area is measured.
Meanwhile, the blood analysis apparatus using the μ-TAS chip has a feature that a small amount of blood can also be analyzed. For this reason, the amount of a measurement liquid obtained by centrifugal separation of blood and mixing and reaction of blood with a reagent also becomes small. When absorbance analysis is performed on this measurement liquid, the measuring area where the measurement liquid is arranged in the μ-TAS chip is a minute region of 1.2 mm×1.2 mm, for example.
In order to make concentrated light enter the measuring area to measure the quantity of light transmitted through the measurement liquid, for example, the diameter of the aperture 23 is about 0.6 mm.
On the other hand, the environmental temperature which surrounds the blood analysis apparatus differs in winter and summer. Due to a change according to this environmental temperature, for example, deformation, such as “expansion/contraction” or “deflection”, may occur in the rotary body 25. When the rotary body is deformed due to a change in an environmental temperature, the position of the aperture 23 shifts with respect to an optical axis extending from the light source to the light-receiving unit 43.
Since the aperture 23 is a minute through hole with a diameter of φ0.6 mm, the amount of the light which enters the aperture 23 lowers extremely if the rotary body 25 with a diameter of φ170 mm is simply deformed slightly.
In addition, in order to prevent the quantity of light which enters the aperture 23 from lowering extremely, it is conceivable to enlarge the diameter of the aperture 23. However, if the aperture 23 is made larger than the measuring area (area where the measurement liquid is located) of the μ-TAS chip, the light from the light source may enter portions other than the measuring area, and thus it becomes impossible to measure only the quantity of light transmitted through the measurement liquid.
As described above, the problem that test results greatly change due to the deformation of the rotary body 25 has been a problem peculiar to the blood analysis apparatus using the μ-TAS chip which perform analysis with a small quantity of blood.
Particularly, in a case where the μ-TAS chip is heated in order to hold the reagent in the μ-TAS chip, and make the reagent and a sample liquid react with each other within the μ-TAS chip, the rotary body holding the μ-TAS chip is also heated. Thus, there is also a problem in that particularly the deformation of the rotary body 25 becomes large.